Thimerosal Attenuates Ischaemia-Reperfusion Arrhythmias in Rats: No Modification by Anti-Ischaemic Agent Trimetazidine or Endothelin Receptor Antagonist Bosentan

Ab, Iskit; Mo, Guc

doi:10.1006/phrs.1996.0058

Cited by 9 publications

(6 citation statements)

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“…24) This effect of thimerosal was independent of the dose, the first time such an effect was observed.…”

Section: Discussionmentioning

confidence: 85%

“…[20][21][22][23] Although thimerosal was effective at blocking the ATP dependent potassium channel, only one study found that it is protective against reperfusion-induced arrhythmia. 24) No study was found indicating that the antiarrhythmia produced by thimerosal depends on blockage of the ATP dependent channel or that another factor is responsible for this protection.…”

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confidence: 99%

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Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

et al. 2005

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SUMMARYThiol-modifying agents induce the release of nitric oxide (NO) from endothelial epithelium and the release of reactive oxygen free radicals in the vascular system. Moreover, thiol groups are essential for the functioning of the ATP dependent potassium channel (K-ATP). The effects of thiol-modifying agents and their molecular mechanisms on arrhythmia have not been widely studied. In this study, we investigated the effect of the hydrophilic SH-group-oxidizing substance thimerosal on the arrhythmia induced by reperfusion/ischemia after coronary artery ligation in rats. We studied the possible involvement of the K-ATP and NOS on the effect of thimerosal. Thimerosal pretreatment (3, 30 mg/kg dose iv. 10 minutes before coronary occlusion) significantly decreased the length of total arrhythmia, ventricular tachycardia, and the arrhythmia score. This effect of thimerosal was reversed by the K-ATP opener pinacidil but not by the K-ATP blocker glibenclamide. The inhibition of iNOS by L-NAME did not alter the antiarrhythmic effect of thimerosal. These data clearly suggest that the antiarrhythmic effect of thimerosal is dependent upon the blockage of K-ATP. ( 1) The activity of some K + channels is drastically altered by the oxidation of critical SH-groups of the channel protein. An interesting example is the loss of rapid inactivation of the voltage-gated K + channel RCK4 (Kv1.4) produced by oxidation of a thiol group; this residue is located near the intracellular inactivation (ball) domain of the channel.2) ATP-sensitive K + channels (K-ATP channels) in skeletal muscle, 3,4) heart 5) and pancreatic β-cells or insulin-secreting cellFrom the

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“…24) This effect of thimerosal was independent of the dose, the first time such an effect was observed.…”

Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

et al. 2005

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“…The mixed ET A \ET B receptor antagonist bosentan did not affect the incidence of reperfusion-induced VF and did not modify infarct size in rats [15]. In another study, bosentan again did not modify the number of ventricular premature beats or the incidence of VF during coronary occlusion or reperfusion in rats [16].…”

Section: Discussionmentioning

confidence: 90%

“…Therefore we employed MAP recording, which is suitable for studying the characteristics of local myocardial repolarization ; moreover, it is one of the most informative and sensitive in vivo electrophysiological methods for the detection of local myocardial ischaemia [17,18]. Ischaemia has several effects on the action potential, namely shortening of MAP duration and decreasing upstroke velocity [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

The ETA receptor antagonist LU 135252 has no electrophysiological or anti-arrhythmic effects during myocardial ischaemia/reperfusion in dogs

et al. 2002

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The anti-arrhythmic effects of ET(A) receptor antagonists during myocardial ischaemia and reperfusion remain controversial. Moreover, the electrophysiological mechanism has not yet been identified. The aim of this study was to investigate the potential anti-arrhythmic and electrophysiological effects of the ET(A) receptor antagonist LU 135252 (LU) during myocardial ischaemia and reperfusion in a canine model. A bolus of LU (1 mg/kg; n=10) or saline (control; n=10) was injected into the left anterior descending coronary artery before ligation of this vessel for 30 min, which was followed by a 90-min reperfusion period. LU bolus administration (0.5 mg/kg) was repeated every 30 min. There were no differences in mean arterial blood pressure or coronary blood flow between the two groups. The determined left ventricular ischaemic mass was 25.5+/-1.8% and 27.8+/-2.2% of the total left ventricular mass in the control and LU groups respectively. The total incidence of ventricular fibrillation during ischaemia and reperfusion was 40% in the control and 50% in the LU group (not significantly different). The incidence of non-sustained and sustained ventricular tachycardias during ischaemia, reperfusion and over the whole period (ischaemia plus reperfusion) in the control group was 50%, 50% and 70% respectively, and that in the LU group was 80%, 70% and 100% respectively (no significant differences between groups). The number of ventricular premature beats was not decreased by LU during either ischaemia or reperfusion [median (25th-75th percentile): ischaemia, 20 (13-37) and 56 (32-130) for LU and control groups respectively; reperfusion, 15 (2-21) and 39 (7-74) respectively; ischaemia+reperfusion, 16 (4-35) and 43 (10-82) respectively; no significant differences between groups]. During ischaemia, the monophasic action potential duration at 90% repolarization (MAPD(90)) decreased significantly, while during reperfusion a significant prolongation of MAPD(90) was observed in the left anterior descending region that was similar in the two groups. In conclusion, LU did not affect repolarization changes and did not have anti-arrhythmic effects during either ischaemia or reperfusion in this model.

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“…MAP recording is one of the most sensitive in vivo electrophysiological methods for the detection of local myocardial ischaemia [10,11]. Changes in MAP duration in the ischaemic area are thought to occur in two ways [12] : the more usual shortened action potential duration of ischaemic cells, and an alternans of action potential in ischaemic cells.…”

Section: Discussionmentioning

confidence: 99%

Expressed monophasic action potential alternans before the onset of ventricular arrhythmias induced by intracoronary bolus administration of endothelin-1 in dogs

et al. 2002

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We showed previously a direct arrhythmogenic effect of the intracoronary infusion of endothelin-1 (ET-1). We aimed to examine the electrophysiological effects of intracoronary bolus administration of ET-1 using monophasic action potential (MAP) recordings. Eight mongrel dogs received boli of ET-1 (1 and 2 nmol) into the left anterior descending coronary artery. These intracoronary ET-1 boli rapidly caused a marked decrease in coronary blood flow (1 nmol, 78+/-7%; 2 nmol, 89+/-7%). Ischaemic changes of MAP morphology, a decrease in upstroke velocity (baseline, 1.78+/-0.2 V/s; 1 nmol, 0.95+/-0.18 V/s; 2 nmol, 0.45+/-0.21 V/s; P<0.01) and a decrease in MAP duration at 90% repolarization (MAPD(90)) [1 nmol, from 191+/-3 to 176+/-5 ms (P<0.05); 2 nmol, from 212+/-4 to 180+/-8 ms (P<0.05)] occurred after ET-1 bolus administration. However, at 7-10 min after the 1 nmol bolus, a significant increase in MAPD(90) was observed (10 min, in the left ventricular anterior epicardial region: from 191+/-3 to 206+/-6 ms; P<0.05). The incidence of ventricular arrhythmias was as follows: after the 1 nmol ET-1 bolus: ventricular tachycardia, 3/8 animals; ventricular fibrillation, 1/8; after the 2 nmol ET-1 bolus: ventricular tachycardia, 5/7; ventricular fibrillation, 5/7. MAP alternans was present in each animal (1 nmol, 18.2+/-5.8%; 2 nmol, 10.8+/-2.5%). Thus electrophysiological and coronary blood flow changes indicate the predominance of an ischaemic arrhythmogenic effect of the bolus administration of ET-1 (shortening of action potential duration; appearance of MAP alternans), whereas the observed delayed prolongation of MAPD(90) suggests a direct arrhythmogenic effect of ET-1. The expressed MAP alternans could have a pathogenic role in the onset of ventricular arrhythmias induced by an intracoronary bolus of ET-1.

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Thimerosal Attenuates Ischaemia-Reperfusion Arrhythmias in Rats: No Modification by Anti-Ischaemic Agent Trimetazidine or Endothelin Receptor Antagonist Bosentan

Cited by 9 publications

References 0 publications

Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

The ETA receptor antagonist LU 135252 has no electrophysiological or anti-arrhythmic effects during myocardial ischaemia/reperfusion in dogs

Expressed monophasic action potential alternans before the onset of ventricular arrhythmias induced by intracoronary bolus administration of endothelin-1 in dogs

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